PDBsum entry 1vzw

Isomerase

PDB id: 1vzw

Contents

Protein chain

224 a.a. *

Ligands

SO4 ×2

GOL

Waters ×226

* Residue conservation analysis

PDB id:

1vzw

Name:

Isomerase

Title:

Crystal structure of the bifunctional protein pria

Structure:

Phosphoribosyl isomerase a. Chain: a. Synonym: 1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino) methylideneamino] imidazole-4-carboxamide isomerase, phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase, n-(5'-phosphoribosyl)anthranilate isomerase, prai. Engineered: yes

Source:

Streptomyces coelicolor. Organism_taxid: 1902. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_variant: neb impact cn.

Resolution:

1.80Å R-factor: 0.164 R-free: 0.205

Authors:

J.Kuper,M.Wilmanns

Key ref:

J.Kuper et al. (2005). Two-fold repeated (betaalpha)4 half-barrels may provide a molecular tool for dual substrate specificity. EMBO Rep, 6, 134-139. PubMed id: 15654319 DOI: 10.1038/sj.embor.7400330

Date:

27-May-04 Release date: 19-Jan-05

Protein chain

P16250  (HIS4_STRCO) -  Phosphoribosyl isomerase A from Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)

Seq: 240 a.a.

Struc: 224 a.a.

Enzyme reactions

• Enzyme class 2: E.C.5.3.1.16 - 1-(5-phosphoribosyl)-5-
• Pathway: Histidine Biosynthesis (early stages)
• Reaction: 1-(5-phospho-beta-D-ribosyl)-5-[(5-phospho-beta-D- ribosylamino)methylideneamino]imidazole-4-carboxamide = 5-[(5-phospho-1- deoxy-D-ribulos-1-ylimino)methylamino]-1-(5-phospho-beta-D- ribosyl)imidazole-4-carboxamide
• Enzyme class 3: E.C.5.3.1.24 - phosphoribosylanthranilate isomerase.

Pathway:

• Reaction: N-(5-phospho-beta-D-ribosyl)anthranilate = 1-(2-carboxyphenylamino)-1- deoxy-D-ribulose 5-phosphate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1038/sj.embor.7400330

EMBO Rep 6:134-139 (2005)

PubMed id: 15654319

Two-fold repeated (betaalpha)4 half-barrels may provide a molecular tool for dual substrate specificity.

J.Kuper, C.Doenges, M.Wilmanns.

ABSTRACT

Some bacterial genomes contain an incomplete set of genes encoding phosphoribosyl isomerases, raising the question of whether there exists broadened substrate specificity for the missing gene products. To investigate the underlying molecular principles of this hypothesis, we have determined the crystal structure of the bifunctional enzyme PriA from Streptomyces coelicolor at 1.8 A resolution. It consists of a (betaalpha)(8)-barrel fold that is assembled by two symmetric (betaalpha)(4) half-barrels. The structure shows how its active site may catalyse the isomerization reactions of two different substrates, and we provide a plausible model of how the smaller of the two substrates could be bound in two different orientations. Our findings expand the half-barrel ancestor concept by demonstrating that symmetry-related half-barrels could provide a smart solution to cope with dual substrate specificity. The data may help to unravel molecular rationales regarding how organisms with miniature genomes can keep central biological pathways functional.

Selected figure(s)

Figure 1.
Figure 1 HisA and TrpF catalyse similar reactions in histidine and tryptophan biosynthesis. HisA and TrpF catalyse the isomerizations of the aminoaldoses ProFAR and PRA to the aminoketoses N'-((5'-phosphoribulosyl)formimino)-5-aminoimidazole-4-carboxamide ribonucleotide (PRFAR) and 1-(o-carboxyphenylamino)-1-deoxyribulose 5-phosphate (CdRP). The PriA protein catalyses both reactions in Streptomyces coelicolor and Mycobacterium tuberculosis. These organisms lack a trpf gene.

Figure 4.
Figure 4 Active site of PriA. (A) Superimposition of the active sites of PriA (blue) and HisA (green). Active-site residues and the two bound sulphate ions are shown in stick mode. The carbon atoms are in the colour of the corresponding C[ ]trace. Oxygen molecules are coloured red and sulphur in yellow. (B) Superimposition of the active sites of PriA (blue) and TrpF (black). Active-site residues and the two bound sulphate ions are shown in stick mode using atom-type colours. (C) PriA active sites with the HisA product analogue rPRFAR. The rPRFAR coordinates have been taken from the superimposed HisF structure (not shown) in the presence of rPRFAR (Chaudhuri et al, 2001). Residues most probably involved in catalysis are highlighted green, surrounded by red circles, in this panel and in all following panels with modelled complexes. (D) PriA active site with the TrpF product analogue rCdRP. The rCdRP coordinates were obtained from the superimposed TrpF structure in complex with rCdRP (Henn-Sax et al, 2002). (E) PriA active site with the TrpF product analogue rCdRP modelled binding to the second phosphate binding site. The rCdRP coordinates were obtained from the TrpF structure in complex with rCdRP (Henn-Sax et al, 2002) superimposed with the C-terminal half-barrel of PriA. Complete PriA was then superimposed using the coordinates obtained from the C-terminal half-barrel. (A -E) Prepared with DINO (http://www.dino3d.org) and rendered with POVRAY 3.6 (http://www.povray.org).

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO Rep (2005, 6, 134-139) copyright 2005.

Figures were selected by an automated process.